Vaccinations and the Risk of Relapse in Multiple Sclerosis
Christian Confavreux, M.D., Samy Suissa, Ph.D., Patricia Saddier, M.D., Ph.D., Valerie Bourdes, M.D., M.P.H., Sandra Vukusic, M.D., for The Vaccines in Multiple Sclerosis Study Group
Background There has been some concern that vaccination mayprecipitate the onset of multiple sclerosis or lead to relapses.Since the recent hepatitis B vaccination program in France,there have been new reports of an increased risk of active multiplesclerosis after vaccination.
Methods We conducted a casecrossover study to assesswhether vaccinations increase the risk of relapse in multiplesclerosis. The subjects were patients included in the EuropeanDatabase for Multiple Sclerosis who had a relapse between 1993and 1997. The index relapse was the first relapse confirmedby a visit to a neurologist and preceded by a relapse-free periodof at least 12 months. Information on vaccinations was obtainedin a standardized telephone interview and confirmed by meansof medical records. Exposure to vaccination in the two-monthrisk period immediately preceding the relapse was compared withthat in the four previous two-month control periods for thecalculation of relative risks, which were estimated with theuse of conditional logistic regression.
Results Of 643 patients with relapses of multiple sclerosis,15 percent reported having been vaccinated during the preceding12 months. The reports of 94 percent of these vaccinations wereconfirmed. Of all the patients, 2.3 percent had been vaccinatedduring the preceding two-month risk period as compared with2.8 to 4.0 percent who were vaccinated during one or more ofthe four control periods. The relative risk of relapse associatedwith exposure to any vaccination during the previous two monthswas 0.71 (95 percent confidence interval, 0.40 to 1.26). Therewas no increase in the specific risk of relapse associated withtetanus, hepatitis B, or influenza vaccination (range of relativerisks, 0.22 to 1.08). Analyses based on risk periods of oneand three months yielded similar results.
Conclusions Vaccination does not appear to increase the short-termrisk of relapse in multiple sclerosis.
Source Information
From the European Database for Multiple Sclerosis Coordinating Center and the Service de Neurologie A, Hôpital Neurologique, Lyons, France (C.C., V.B., S.V.); the Division of Clinical Epidemiology, Royal Victoria Hospital, and the Department of Epidemiology and Biostatistics, the Department of Medicine, and the McGill Pharmacoepidemiology Research Unit, McGill University, Montreal (S.S.); and the Department of Epidemiology, Aventis Pasteur, Lyons, France (P.S.).
Address reprint requests to Dr. Confavreux at the EDMUS Coordinating Center, Hôpital Neurologique, 59 blvd. Pinel, 69394 Lyons CEDEX 03, France.
Stassen, P. M., Kallenberg, C. G. M., Stegeman, C. A.
(2009). Reply. Nephrol Dial Transplant
24: 3259-3259
[Full Text]
Ness, J. M., Bale, J. F. Jr
(2009). Hepatitis vaccines and pediatric multiple sclerosis: Does timing or type matter?. Neurology
72: 870-871
[Full Text]
'Chris' Delaney, J. A, Suissa, S.
(2009). The case-crossover study design in pharmacoepidemiology. Stat Methods Med Res
18: 53-65
[Abstract]
Djeriri, K., Laurichesse, H., Merle, J. L., Charof, R., Abouyoub, A., Fontana, L., Benchemsi, N., Elharti, E., El Aouad, R., Chamoux, A., Beytout, J.
(2008). Hepatitis B in Moroccan health care workers. Occup Med (Lond)
58: 419-424
[Abstract][Full Text]
Stassen, P. M., Sanders, J.-S. F., Kallenberg, C. G. M., Stegeman, C. A.
(2008). Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol Dial Transplant
23: 654-658
[Abstract][Full Text]
Mikaeloff, Y., Caridade, G., Assi, S., Tardieu, M., Suissa, S., on behalf of the KIDSEP study group of the French,
(2007). Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination. Brain
130: 1105-1110
[Abstract][Full Text]
Hernan, M. A., Alonso, A., Hernandez-Diaz, S.
(2006). Tetanus vaccination and risk of multiple sclerosis: a systematic review.. Neurology
67: 212-215
[Abstract][Full Text]
Minden, S L, Frankel, D, Hadden, L, Perloff, J, Srinath, K P, Hoaglin, D C
(2006). The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics. Mult Scler
12: 24-38
[Abstract]
Schwid, S. R., Decker, M. D., Lopez-Bresnahan, M., for the Rebif-Influenza Vaccine Study Investigator,
(2005). Immune response to influenza vaccine is maintained in patients with multiple sclerosis receiving interferon beta-1a. Neurology
65: 1964-1966
[Abstract][Full Text]
Leary, S M, Porter, B, Thompson, A J
(2005). Multiple sclerosis: diagnosis and the management of acute relapses. Postgrad. Med. J.
81: 302-308
[Abstract][Full Text]
Poland, G. A., Jacobson, R. M.
(2004). Prevention of Hepatitis B with the Hepatitis B Vaccine. NEJM
351: 2832-2838
[Full Text]
Naismith, R. T., Cross, A. H.
(2004). Does the hepatitis B vaccine cause multiple sclerosis?. Neurology
63: 772-773
[Full Text]
Karayiannis, P., Main, J., Thomas, H. C.
(2004). Hepatitis vaccines. Br Med Bull
70: 29-49
[Full Text]
DeStefano, F., Verstraeten, T., Jackson, L. A., Okoro, C. A., Benson, P., Black, S. B., Shinefield, H. R., Mullooly, J. P., Likosky, W., Chen, R. T.
(2003). Vaccinations and Risk of Central Nervous System Demyelinating Diseases in Adults. Arch Neurol
60: 504-509
[Abstract][Full Text]
Offit, P. A., Hackett, C. J.
(2003). Addressing Parents' Concerns: Do Vaccines Cause Allergic or Autoimmune Diseases?. Pediatrics
111: 653-659
[Abstract][Full Text]
Etienney, I, Beaugerie, L, Viboud, C, Flahault, A
(2003). Non-steroidal anti-inflammatory drugs as a risk factor for acute diarrhoea: a case crossover study. Gut
52: 260-263
[Abstract][Full Text]
Ki, M., Park, T., Yi, S. G., Oh, J. K., Choi, B.
(2003). Risk Analysis of Aseptic Meningitis after Measles-Mumps-Rubella Vaccination in Korean Children by Using a Case-Crossover Design. Am J Epidemiol
157: 158-165
[Abstract][Full Text]
Rutschmann, O. T., McCrory, D. C., Matchar, D. B.
(2002). Immunization and MS: A summary of published evidence and recommendations. Neurology
59: 1837-1843
[Abstract][Full Text]
Lorber, B.
(2002). Update in Infectious Diseases. ANN INTERN MED
137: 974-980
[Full Text]
Havinga, W., Offit, P. A., Gerber, M. A., Hackett, C., Marcuse, E., Gellin, B.
(2002). Too Many Vaccinations?. Pediatrics
110: 648-649
[Full Text]
Belloni, C., Avanzini, M. A., De Silvestri, A., Martinetti, M., Pasi, A., Coslovich, E., Autelli, M., Masanti, M. L., Cuccia, M., Tinelli, C., Rondini, G., Lorini, R.
(2002). No Evidence of Autoimmunity in 6-Year-Old Children Immunized at Birth With Recombinant Hepatitis B Vaccine. Pediatrics
110: e4-4
[Abstract][Full Text]
Sibilia, J, Maillefert, J F
(2002). Vaccination and rheumatoid arthritis. Ann Rheum Dis
61: 575-576
[Full Text]
Confavreux, C.
(2002). Infections and the risk of relapse in multiple sclerosis. Brain
125: 933-934
[Full Text]
Buljevac, D., Flach, H. Z., Hop, W. C. J., Hijdra, D., Laman, J. D., Savelkoul, H. F. J., van der Meche, F. G. A., van Doorn, P. A., Hintzen, R. Q.
(2002). Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain
125: 952-960
[Abstract][Full Text]
Burt, R. K., Slavin, S., Burns, W. H., Marmont, A. M.
(2002). Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?. Blood
99: 768-784
[Abstract][Full Text]
Ahmed, F., Singleton, J. A., Franks, A. L.
(2001). Influenza Vaccination for Healthy Young Adults. NEJM
345: 1543-1547
[Full Text]
Dennehy, P. H.
(2001). Active Immunization in the United States: Developments over the Past Decade. Clin. Microbiol. Rev.
14: 872-908
[Abstract][Full Text]
Begaud, B., Alperovitch, A., Hanslik, T., Viboud, C., Flahault, A., Gout, O., Sturkenboom, M. C.J.M., Fourrier, A., Buttinelli, C., Salvetti, M., Ristori, G., Hostetler, L., Ascherio, A., Zhang, S. M., Walker, A. M., Confavreux, C., Suissa, S., Saddier, P.
(2001). Vaccinations and Multiple Sclerosis. NEJM
344: 1793-1796
[Full Text]
Rathore, M. H.
(2001). Guillain-Barre Syndrome Not Related to MMR. AAP Grand Rounds
5: 46-47
[Full Text]
(2001). No Significant Risk to Vaccination in MS. JWatch Neurology
2001: 1-1
[Full Text]
(2001). From Rumor to Reality: Vaccinations Not Associated with MS Onset or Relapse. JWatch Infect. Diseases
2001: 1-1
[Full Text]
(2001). No Link Between Vaccination and Multiple Sclerosis. JWatch General
2001: 1-1
[Full Text]
Gellin, B. G., Schaffner, W.
(2001). The Risk of Vaccination -- The Importance of "Negative" Studies. NEJM
344: 372-373
[Full Text]
DeStefano, F., Verstraeten, T., Newman, J.P., Noseworthy, J. H., Poland, G. A.
(2001). Multiple Sclerosis. NEJM
344: 381-382
[Full Text]